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Copper transport drug restores memory and clears toxic Alzheimer's proteins

monash.edu

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Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#41

Post by jjtheblunt »

uxhacker wrote: post #38
fnordpiglet wrote: post #25

Earlier quoted context omitted.

No actually there’s a large body of quashed research over these decades that went against the prevailing hypothesis. It’s one of the key examples of how peer review fails to consider novel approaches in the face of consensus even if consensus is shown to likely be wrong. The fact the original research driving the consensus was fraudulent at worst made it that much more sad. To be clear this isn’t about whether it’s r…

Groupthink is very much the scientific method. According to Imre Lakatos the key question is does the group expand knowledge or contract it (very rushed reply as about to catch a flight)

Proofs and Refutations is a great book

https://a.co/d/0cXTgHgv

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#42

Post by bigbuppo »

dekhn wrote: post #34
cassepipe wrote: post #23

Earlier quoted context omitted.

This is just one person's (informed I assume) opinion tough. It does sound like common sense but alas common sense is rarely a good guide when it comes down to how the body works. I don't have a dog in this fight and I don't remember that much but I read someone's "in defense of the amyloid hypothesis" with interest. So if you want an counterpoint, you can go read https://www.astralcodexten.com/p/in-defense-of-the-am…

If I had to choose between Derek Lowe (author of the anti-amyloid-research article who is also highly experienced and skilled in pharma) and Scott Alexander/David Schneider-Joseph (psychiatrist and AI engineer, respectively), all my priors suggest Lowe gives better advice. "I am David Schneider-Joseph, an engineer formerly with SpaceX and Google, now working in AI safety. Alzheimer’s isn’t my field, but I got very in…

I'm pretty sure there's an xkcd for this.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#43

Post by dekhn »

selimthegrim wrote: post #37
dekhn wrote: post #34

Earlier quoted context omitted.

If I had to choose between Derek Lowe (author of the anti-amyloid-research article who is also highly experienced and skilled in pharma) and Scott Alexander/David Schneider-Joseph (psychiatrist and AI engineer, respectively), all my priors suggest Lowe gives better advice. "I am David Schneider-Joseph, an engineer formerly with SpaceX and Google, now working in AI safety. Alzheimer’s isn’t my field, but I got very in…

This really has become the new physics now, right where they think they can invade any given field in six months because that’s how long it’s supposed to take physicists to learn AI

In some ways physics is different from biology and medicine, I do think outsiders to physics can pick up and contribute a bit more easily (although it depends on field). Biomed just has an absolute insane amount of ambiguous knowledge that mostly gets picked up through diffusion across decades of learning. And many of the results in the literature are just wrong (one of the reasons I stopped being a researcher was seeing just how bad the publication record in biology is).

BTW, many physics people pick up the mechanical bits of machine learning/AI very quickly since they have all the foundational mathematics. The harder parts are understanding all the methods/tricks/complexity that got us to the state of the art- similar to biomed, you just sort of have to immerse yourself amongst knowledgeable people and let their knowledge diffuse in.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#44

Post by DavidSJ »

dekhn wrote: post #34
cassepipe wrote: post #23

Earlier quoted context omitted.

This is just one person's (informed I assume) opinion tough. It does sound like common sense but alas common sense is rarely a good guide when it comes down to how the body works. I don't have a dog in this fight and I don't remember that much but I read someone's "in defense of the amyloid hypothesis" with interest. So if you want an counterpoint, you can go read https://www.astralcodexten.com/p/in-defense-of-the-am…

If I had to choose between Derek Lowe (author of the anti-amyloid-research article who is also highly experienced and skilled in pharma) and Scott Alexander/David Schneider-Joseph (psychiatrist and AI engineer, respectively), all my priors suggest Lowe gives better advice. "I am David Schneider-Joseph, an engineer formerly with SpaceX and Google, now working in AI safety. Alzheimer’s isn’t my field, but I got very in…

This frequently comes up as a critique of my article, but I don't claim to be disrupting the field as a smart outsider. Rather, I looked at the field and concluded that the experts seem to know what they're doing. Derek Lowe is very much in the minority on this matter.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#45

Post by biomcgary »

uxhacker wrote: post #38
fnordpiglet wrote: post #25

Earlier quoted context omitted.

No actually there’s a large body of quashed research over these decades that went against the prevailing hypothesis. It’s one of the key examples of how peer review fails to consider novel approaches in the face of consensus even if consensus is shown to likely be wrong. The fact the original research driving the consensus was fraudulent at worst made it that much more sad. To be clear this isn’t about whether it’s r…

Groupthink is very much the scientific method. According to Imre Lakatos the key question is does the group expand knowledge or contract it (very rushed reply as about to catch a flight)

In Lakatosian terms, the amyloid hypothesis is an example of a degenerating research program that has largely failed to predict new observations and is primarily driven by post hoc reasoning. The hypothesis was rescued by research claiming a significant new observation that was ultimately shown to be fraudulent (https://pmc.ncbi.nlm.nih.gov/articles/PMC12397490/).

From a Lakatosian perspective, the amyloid hypothesis is not necessarily wrong, but it is not paying off in terms of empirical insights relative to the amount of attention and funding it has received.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#46

Post by nphardon »

avgDev wrote: post #19

My mother has early onset alzheimer's disease. We currently know very little about the disease and the current treatment options are controversial. The efficacy of the medications removing the amyloid plaque from the brain is questionable, as people still decline. What makes alzheimer's difficult is that it is not really a single uniform disease. There are subtypes. Since my mother has it, I was presented with an opt…

How old is your mother? Iirc PSEN1 correlates to very early AD, like late 30s early 40s. My dad had full blown AD at 65, with serious cognitive decline starting at 63, and that felt very early to us all. My dad had no AD biomarkers on full genetic scan. My heart goes out to you and your family.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#47

Post by mannyv »

Anything that might fix brain plumbing would be welcome.

Over time, everything breaks down. If this actually fixes some plumbing issue that would be great. Of course, it probably will lead to another downstream plumbing issue, but one thing at a time.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#48

Post by pengaru »

mlmonkey wrote: post #36

In some parts of the world, it is recommended that drinking water be stored in copper containers. I'm wondering if these communities had figured something out about the health benefits of ingesting trace amounts of copper?

There's no need for missing answers as to why copper is appreciated as a water transport/storage medium. It's the same reason it's traditionally used as cladding on boat hulls, and is still added to many anti-fouling bottom paints - it's antimicrobial, but also toxic.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#49

Post by bluGill »

mimicmagnet wrote: post #35
dgoldstein0 wrote: post #32

Earlier quoted context omitted.

> Over 56 days, the treatment reduced toxic amyloid-beta by 42 per cent and improved spatial learning by nearly 44 per cent So there's some benefit. Sounds like their next step is a much larger trial to answer the question you are posing.

https://pubs.acs.org/doi/10.1021/acschemneuro.6c00252 In mice. This is a repeating trend in Alzheimer's research, where the amyloid-beta treatment works in the mouse model but not on humans, because the mouse model induces the amyloid-beta issue (mice don't really get Alzheimer's) and then we treat it.

It is a repeating trend in all medical research. However enough does turn out to work in humans that we eventually make useful progress.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#50

Post by MarkusQ »

cassepipe wrote: post #23
quadhome wrote: post #5

Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta. In the words of Derek Lowe: Amyloid-directed therapies truly, truly do not appear to be the answer for Alzheimer’s treatment. When I started work in the field back in the early 1990s, I was convinced of the opposite - the evidence looked very strong that defects in amyloid processing were indeed the cause of the disease. But that was thirty-f…

This is just one person's (informed I assume) opinion tough. It does sound like common sense but alas common sense is rarely a good guide when it comes down to how the body works. I don't have a dog in this fight and I don't remember that much but I read someone's "in defense of the amyloid hypothesis" with interest. So if you want an counterpoint, you can go read https://www.astralcodexten.com/p/in-defense-of-the-am…

> Alzheimer’s isn’t my field, but I got very interested in it, spent six months studying the literature, and came away believing the amyloid hypothesis was basically completely solid.

If the accusation is "the field has been captured by a group with a vested interest in a model based on fraudulent research, strongly biasing what gets funded and what gets published" I wouldn't expect "studying the literature" to be particularly helpful in assessing the claim. It's sort of like saying "I read all of Enron's press releases and SEC filings, and they sound legit."

The defense reads more like a special pleading or sunk cost fallacy. There has been a lot of research done on one hypothesis, actively excluding alternatives, so that hypothesis deserves to be considered until disproven (he does, iirc, allow for a test that would de-privilege the amaloyd hypothesis).

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